Fig. 3.

Deletion of grp94 in mouse results in compromise of gut homeostasis and loss of Wnt coreceptor LRP6. (A) Percent weight changes in WT and grp94 KO mice 12 d PTI. (B) Gross pathology showing bowel dilatation (∼three times of the diameter of the WT mice), obstruction, edema, and hemorrhage in the small intestine of grp94 KO mice (one representative mouse over more than 120 is shown). (C) H&E staining of gut sections of grp94 WT and grp94 KO mice 12 d PTI. The KO mice have fewer and shorter villi, especially in the ileum, which shows almost complete loss of villi with marked reduction of crypt. Multiple experiments (more than 30) were done with similar findings. (Scale bar: 100 μm.) (D) Quantification of gut pathology of KO (n = 5) and WT (n = 6) mice 12 d PTI. *P < 0.05. (E) Lysozyme stain of Paneth cells in the crypts of the ileum section. There was loss of crypt-villus structure and absence of Paneth cells in the KO ileum. (F) Immunofluorescence for BrdU and DAPI in the ileum of untreated (UT) and 12-d tamoxifen-treated mice. (Scale bar: 100 μm.) Comparing to the ileum of untreated mice, the tamoxifen-treated mice show significant loss of villi and crypts with markedly decreased BrdU uptake in the crypt. (G) Immunoblot for endogenous LRP6 at day 0 (WT mice) and day 12 (grp94 KO mice). grp94 and β-actin (loading control) expression is shown.